DESCRIPTION: There are critical periods during pregnancy when developmental and organizational processes are vulnerable to perturbations. These critical periods are characterized by rapid changes in specific events. The rapid increase in corticotrophic-releasing-hormone (CRH) beginning in the early second trimester and continuing until term defines a critical period when the length of gestation may be vulnerable to the effects of stress. Close associations among stress and the hypothalamic-pituitary-adrenal-placental (HPAP) axis during the third trimester were discovered during our initial project, and both of these factors, independently, influenced the timing of delivery. Preliminary evidence from our project indicated the HPAP axis activation, especially CRH, and perhaps prenatal stress, exerted a greater influence during midgestation than during late third trimester on the timing of delivery. Extension of these new findings may have profound significance because preterm birth is the major cause of infant mortality and morbidity in the United States. The central objective of this proposal is to determine if there are critical periods of vulnerability to psychosocial stress and to activation of the HPAP axis during human pregnancy that influence the length of gestation. The first aim is to determine the relationship between maternal psychosocial stress, specifically during mid-gestation, its rate of change to term and the risk for preterm delivery. The second aim is to determine the relationship between maternal psychosocial stress, specifically during mid-gestation, and the rate of CRH increase (slope) over the latter part of gestation. The third aim is to determine when, during the second and third trimester, the effects of stress are maximal on response of the maternal/placental neuroendocrine axis. The fourth aim is to determine if the effects of psychosocial stress on the duration of gestation will be greater in mid-gestation (20-22 weeks) than later in gestation (32-34 weeks). The fifth aim is to quantify and contrast placental CRHmRNA activity in term and preterm and high and low stress pregnancies with in situ hybridization studies. These objectives will be achieved by collecting longitudinal data on an ethnically-diverse sample of 500 women at high medical risk for preterm delivery (PTD; yielding 100+ preterm births) and 110 women at low risk for PTD recruited before 18 to 20 weeks gestation. Psychosocial interviews will be conducted and endocrine concentrations will be determined at 20 to 22 weeks (mid-gestation), 26 to 28 weeks (early third trimester), and 32 to 34 weeks (mid-third trimester) gestation, and at 10 to 12 weeks postpartum. The study design and analytic methods allows for estimation of the unique effects of CRH and psychosocial stress on the length of gestation.